With the global supply chain—and a large amount of secrecy—involved with manufacturing modern pharmaceuticals, maintaining standards and enforcing safety requirements appears to be challenging the FDA’s monitoring capacity. In November 2018, Scott Gottlieb, MD, then commissioner of the FDA and current resident fellow at the American Enterprise Institute, told USA Today, “We put out very big guidance on this—it’s a known risk. It’s a place where there’s been a significant increase in focus in recent years.”

“Since the start of 2013, pharmaceutical companies based in
the US or abroad have recalled about 8,000 medicines, comprising billions of
tablets, bottles, and vials that have entered the US drug supply and made their
way to patients ….” KHN reported. “Over
the same period, 65 drug-making facilities recalled nearly 300 products within
12 months of passing [an FDA] inspection ….”

Data published by Stericycle Expert Solutions, a global B2B services company, offers deeper insight into forces driving recalls in Q3 of 2018. “Pharmaceutical recalls increased 19% to 92—the second highest quarter since Q3 2013,” they note. “Failed specifications were the top reason based on recalls for the ninth consecutive quarter.”

Current Good Manufacturing Practices (CGMPs) ranked second, accounting for 23.9% of recalls in their study. The same data shows medical device recalls also increased across 2018 compared to the prior year.

In an e-mail to Kaiser Health News, FDA spokesman Jeremy Kahn said, “While the FDA would prefer that no drug be distributed that later is recalled, we do not think that a recall indicates a failure of FDA inspection and surveillance programs.” He continued, noting that inspectors “may not uncover all issues or practices that may eventually result in a problem leading to a recall” and that “not all recalls are the result of poor manufacturing practice.” (Graphic and caption copyright: Kaiser Health News.)

Issues now presented as “shortcomings” with pharmaceutical oversight could one day present serious concerns for pathology groups, clinical laboratories, and other service providers using IVDs.

In a field requiring precision, quality, and accuracy to provide
reliable results for an ever-growing portion of modern healthcare’s questions, quality
control of testing materials and devices is critical—particularly when dealing
with the increasingly smaller samples and sensitive reagents used today.

Enforcing Standards
Around the World

Despite today’s CGMPs and myriad regulations designed to ensure
pharmaceuticals are safe, KHN notes
that the FDA struggles to stay ahead of manufacturers and suppliers who might
violate regulations. Even when FDA inspectors discover issues, they have little
means of enforcing standards and encouraging change.

“A KHN review of
thousands of FDA documents—inspection records, recalls, warning letters and
lawsuits—offers insight into the ways poorly manufactured or contaminated drugs
reach consumers,” KHN notes. “Inspectors
miss serious hazards. Drug makers fail to meet standards even after the FDA has
taken enforcement action. Hundreds of plants haven’t been inspected for years,
if ever.”

However, no amount of protective regulations or standards can
make a significant impact without proper enforcement. In October 2017, the FDA
announced they would recognize the European drug regulatory authorities of
eight countries to help reduce duplicative inspection. “By partnering with
these countries,” said Gottlieb, “we can create greater efficiencies and better
fulfill our public health goals, relying on the expertise of our colleagues and
refocusing our resources on inspections in higher risk countries.”

Nonetheless, statistics indicate that the FDA’s ability to support
global inspections is still stretched thin. More than 2,500 foreign and
domestic facilities have not received a drug-quality inspection in more than
five years, according to KHN. Additionally,
1,200 domestic facilities and 400 foreign facilities were found to have no
drug-quality inspection records dating back 10 years, KHN reported.

While Gottlieb hopes to “clear the backlog” by the end of
September 2019, the fact that such a backlog exists at all is cause enough for
concern—particularly in light of Gottlieb’s
April 2019 resignation, KHN
noted.

Even with an effective inspection system, the FDA’s options
for bringing manufacturers into compliance are limited. KHN points out that over the past decade, 70 plants in their data
sets received citations for the same violation four or more times. The FDA
cannot issue mandatory
recalls, and while it can seize drug products, it has only exercised that
right 23 times in the past decade. This shows how few options the FDA has for
ensuring contaminated or otherwise defective medications do not reach patients,
hospitals, and other part of the healthcare industry.

For anatomic
pathologists, clinical laboratories, and other diagnosticians relying on the
FDA to be the gatekeeper of quality and safety—as well as ensuring IVDs provide
accurate, reproducible results—these trends in pharmaceutical oversight should be
cause for concern.

Worse still, the lack of effective enforcement options
available to inspectors and oversight committees—alongside the sheer scale of a
global manufacturing chain—offer few easy answers for reversing the trends
making headlines today.